The control of the cell cycle, during which cells replicate their DNA and divide, is a cardinal step in normal human cell growth and in tissue differentiation, while de-regulation of this process can result in tumourigenesis and the onset of cancer. Protein-protein interactions play a crucial role in these events, with the regulation of gene expression in particular being central for the determination of cell cycle fate.
Recently, the transcriptional co-factor CBP (CREB binding protein) and the related protein p300 have been implicated in the control of cell cycle events. Interestingly, CBP has been shown to be required for both E2F activity which results in the expression of S phase specific genes and cellular proliferation, and for the expression of p21WAF by p53, which results in cell cycle arrest. Moreover, studies of cellular transformation by the adenovirus oncogene product E1A have shown that an interaction with CBP is necessary for this process. These observations suggest that two opposite cell cycle events rely upon an interaction with a common factor, CBP/p300.
CBP is a very large protein (2,441 amino acids) and can be thought of as a transcriptional adaptor with the capability of binding many different transcriptional factors. While a few regions of CBP have been described a “hot spots” for protein interactions, the mechanisms by which different proteins interact with CBP, and the exact motifs involved, have not been defined. Many of the proteins that regulate the cell cycle bind to the same 257 amino acid region of CBP (1621-1877). However, since a number of these proteins are thought to have antagonist effects, it would be useful to know if the same CBP sequences were recognized by these different proteins or if not, if the different motifs overlapped.